Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex

ELife
Maria M DiehlGregory J Quirk

Abstract

Much is known about the neural circuits of conditioned fear and its relevance to understanding anxiety disorders, but less is known about other anxiety-related behaviors such as active avoidance. Using a tone-signaled, platform-mediated avoidance task, we observed that pharmacological inactivation of the prelimbic prefrontal cortex (PL) delayed avoidance. Surprisingly, optogenetic silencing of PL glutamatergic neurons did not delay avoidance. Consistent with this, inhibitory but not excitatory responses of rostral PL neurons were associated with avoidance training. To test the importance of these inhibitory responses, we optogenetically stimulated PL neurons to counteract the tone-elicited reduction in firing rate. Photoactivation of rostral (but not caudal) PL neurons at 4 Hz impaired avoidance. These findings suggest that inhibitory responses of rostral PL neurons signal the avoidability of a potential threat and underscore the importance of designing behavioral optogenetic studies based on neuronal firing responses.

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Citations

Jul 26, 2018·The European Journal of Neuroscience·Maria M DiehlDavid V Smith
Sep 28, 2018·Psychopharmacology·Freddyson J Martínez-RiveraGregory J Quirk
Aug 22, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Luis E Rosas-VidalGregory J Quirk
Jul 6, 2020·Translational Psychiatry·Freddyson J Martínez-RiveraGregory J Quirk
Jun 26, 2020·Nature Communications·Tomer GazitItzhak Fried
Jul 19, 2019·Neuron·Drew B HeadleyDenis Paré
Oct 10, 2020·Neuroscience and Biobehavioral Reviews·Elizabeth E ManningMihaela D Iordanova
Jan 16, 2020·Biological Psychiatry·Lindsay R HalladayAndrew Holmes
Jun 13, 2020·Behavioural Brain Research·Lucas R GloverAndrew Holmes
Mar 16, 2021·Frontiers in Neuroscience·Hector Bravo-RiveraGregory J Quirk
Jun 28, 2021·Behavioural Brain Research·Vincent D Campese
Jul 16, 2021·Nature·Daniel JercogCyril Herry

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